Faculty Bibliography

BACKGROUND:or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS:We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS:Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, -0.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, -2.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, -1.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, -2.2 to 3.4). CONCLUSIONS:Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy. (Funded by the National Heart, Lung, and Blood Institute; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).

Background Women have been associated with higher rates of recurrent events after percutaneous coronary intervention than men, possibly attributable to advanced age at presentation and greater comorbidities. These factors also put women at higher risk of bleeding, which may influence therapeutic strategies and clinical outcomes. Methods and Results We performed a patient-level pooled analysis of 4 postapproval registries to evaluate sex-related differences in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention. HBR required fulfillment of at least 1 major or 2 minor criteria of the Academic Research Consortium definition. Outcomes of interest were major bleeding and major adverse cardiac events (composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis). Of the total 10 502 patients, 2832 (27.0%) were women. The prevalence of HBR was higher in women compared with men (29.0% versus 20.5%, P<0.0001). Women at HBR were older and had more comorbidities, while men at HBR were more often smokers, with prior myocardial infarction and more complex coronary lesions. At 4 years, women at HBR had significantly higher major bleeding compared with men at HBR (10.8% versus 6.2%, P<0.0001); however, this difference was attenuated after multivariable adjustment (hazard ratio, 0.92; 95% CI, 0.41-2.08). Major adverse cardiac event rates between groups were similar (12.2% versus 12.6%, P=0.82) and remained consistent after adjustment (hazard ratio, 0.64; 95% CI, 0.32-1.28). Conclusions The prevalence of HBR was higher in women compared with men, with considerable differences in the distribution of criteria. Women at HBR experienced higher rates of major bleeding but similar major adverse cardiac event rates compared with men at HBR at 4 years.

Background: Long-term outcomes in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent are unclear. Therefore, we aimed to evaluate long-term adverse events in HBR patients undergoing PCI with cobalt-chromium (CoCr) everolimus-eluting stent implantation. Methods: We analyzed stratified data from four all-comers post-approval registries. Patients with at least one of the following criteria were categorized as HBR: age ≥75 years, history of major bleeding (MB), history of stroke, chronic oral anticoagulant use, chronic kidney disease (CKD), anemia, or thrombocytopenia. Additionally, in a separate analysis, patients were categorized according to the recently published Academic Research Consortium (ARC) HBR criteria. The Kaplan-Meier method was used for time-to-event analyses. Coronary thrombotic events (CTE) included myocardial infarction or definite/probable stent thrombosis. MB was defined according to the TIMI or GUSTO scales. Impact of CTE and MB on subsequent risk of mortality was assessed using multivariable Cox regression with MB and CTE included as time-updated covariates. Results: Of the total 10,502 patients included, 3,507 (33%) were identified as HBR. Compared to non-HBR patients, those at HBR had more comorbidities, higher lesion complexity and a higher risk of 4-year mortality (HR 4.38, 95% CI 3.76-5.11). Results were qualitatively similar when using ARC criteria to define HBR. Risk of mortality was increased after CTE (HR 5.02, 95% CI 3.93-6.41), as well as after MB (HR 4.92, 95% CI 3.82-6.35). Of note, this effect was consistent across the spectrum of bleeding risk (p-interaction test 0.97 and 0.06, respectively). Conclusions: Compared to the non-HBR population, HBR patients experienced worse 4-year outcomes after PCI with CoCr everolimus-eluting stent. Both CTE and MB had a significant impact on subsequent risk of mortality irrespective of bleeding risk.

BACKGROUND:Patients on long-term dialysis are at increased risk of bleeding. Although oral anticoagulants (OACs) are recommended for atrial fibrillation (AF) to reduce the risk of stroke, randomized trials have excluded these populations. As such, the net clinical benefit of OACs among patients on dialysis is unknown. OBJECTIVES/OBJECTIVE:This study aimed to investigate the efficacy and safety of OACs in patients with AF on long-term dialysis. METHODS:MEDLINE and EMBASE were searched through June 10, 2019, for studies that investigated the efficacy and safety of different OAC strategies in patients with AF on long-term dialysis. The efficacy outcomes were ischemic stroke and/or systemic thromboembolism, all-cause mortality, and the safety outcome was major bleeding. RESULTS:This study identified 16 eligible observational studies (N = 71,877) regarding patients on long-term dialysis who had AF. Only 2 of 16 studies investigated direct OACs. Outcomes for dabigatran and rivaroxaban were limited to major bleeding events. Compared with no anticoagulants, apixaban and warfarin were not associated with a significant decrease in stroke and/or systemic thromboembolism (apixaban 5 mg, hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.30 to 1.17; apixaban 2.5 mg, HR: 1.00; 95% CI: 0.52 to 1.93; warfarin, HR: 0.91; 95% CI: 0.72 to 1.16). Apixaban 5 mg was associated with a significantly lower risk of mortality (vs. warfarin, HR: 0.65; 95% CI: 0.45 to 0.93; vs. apixaban 2.5 mg, HR: 0.62; 95% CI: 0.42 to 0.90; vs. no anticoagulant, HR: 0.61; 95% CI: 0.41 to 0.90). Warfarin was associated with a significantly higher risk of major bleeding than apixaban 5 min/2.5 mg and no anticoagulant (vs. apixaban 5 mg, HR: 1.41; 95% CI: 1.07 to 1.88; vs. apixaban 2.5 mg, HR: 1.40; 95% CI: 1.07 to 1.82; vs. no anticoagulant, HR: 1.31; 95% CI: 1.15 to 1.50). Dabigatran and rivaroxaban were also associated with significantly higher risk of major bleeding than apixaban and no anticoagulant. CONCLUSIONS:This meta-analysis showed that OACs were not associated with a reduced risk of thromboembolism in patients with AF on long-term dialysis. Warfarin, dabigatran, and rivaroxaban were associated with significantly higher bleeding risk compared with apixaban and no anticoagulant. The benefit-to-risk ratio of OACs in patients with AF on long-term dialysis warrants validation in randomized clinical trials.

For patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI), antithrombotic therapy including oral anticoagulants and antiplatelets are indicated. The optimal combination is not known. We investigated the efficacy and safety of different antithrombotic strategies in patients with AF undergoing PCI. PUBMED and EMBASE were searched through September 2019 for randomized trials investigating the efficacy and safety of different antithrombotic strategies in patients with AF who underwent PCI and/or acute coronary syndrome. Nine antithrombotic strategies were compared including combinations of vitamin K antagonist (VKA) with dual antiplatelet therapy (DAPT) or P2Y₁₂ inhibitor, combinations of direct oral anticoagulants (DOAC) (apixaban, dabigatran, rivaroxaban, and edoxaban) with DAPT or P2Y₁₂ inhibitor (clopidogrel, prasugrel, and ticagrelor). The primary safety outcome was trial defined primary bleeding outcome. The primary efficacy outcome was trial defined major adverse cardiovascular events. Our search identified 5 eligible trials that enrolled a total of 11,532 patients and compared 9 treatment strategies. VKA + DAPT significantly increased bleeding when compared with most combinations (for example, vs VKA + P2Y₁₂ inhibitor: odds ratio 2.11; 95% confidence interval [1.76 to 2.52], p <0.001). Of all the combinations, apixaban + P₂Y₁₂ inhibitor showed the lowest bleeding risk (for example, vs VKA + P2Y₁₂ inhibitor: odds ratio 0.63; 95% confidence interval [0.51 to 0.78], p <0.001) and was ranked the best treatment. There were no significant differences in ischemic outcome of major adverse cardiovascular events between various antithrombotic regimens. In conclusion, in patients with AF undergoing PCI, apixaban + P2Y₁₂ inhibitors were associated with lowest bleeding compared with other regimens including other DOACs + P2Y₁₂ inhibitors with no increase in ischemic outcomes.

The aim of the study was to evaluate the outcomes with completeness of revascularization (CR) in patients with multivessel disease (MVD) who underwent PCI using everolimus-eluting stent (EES). Patients with MVD who underwent PCI using EES in New York State were chosen. Patients were categorized into CR, attempted but failed CR or incomplete revascularization (ICR). The primary outcome was death/myocardial infarction (MI). Secondary outcomes were death/MI/repeat revascularization and the individual components of the composite outcomes. Multiple propensity score adjustment analysis was used to adjust for differences in covariates among the 3 groups. Among 15,046 patients, 4,545 (30%) had CR. The strongest predictors of ICR were the number of vessels diseased (χ²â€¯= 428.48; p <0.0001) and presence of chronic total occlusion (CTO) (χ²â€¯= 184.27; p <0.0001). In the multiple propensity score-adjusted analysis, over a mean follow-up of 2.9 years, compared with CR, ICR was associated with significant higher risk of death/MI (17.49% vs 12.69%; hazard ratio [HR] = 1.15; 95% confidence interval [CI] 1.02 to 1.29; p = 0.02), death/MI/repeat revascularization (48.01% vs 37.85%; HR = 1.19; 95% CI 1.12 to 1.27; p <0.0001), death (12.41% vs 8.63%; HR = 1.16; 95% CI 1.00 to 1.35; p = 0.047), and repeat revascularization (39.16% vs 31.63%; HR = 1.20; 95% CI 1.12 to 1.28; p <0.0001), with numerically higher rates of MI (7.18% vs 4.90%; HR = 1.17; 95% CI 0.98 to 1.40; p = 0.09). The risk with attempted but failed CR was intermediate between CR and ICR. In conclusion, in patients with MVD who underwent PCI with EES, incomplete revascularization is associated with significantly higher risk of cardiovascular events including death compared with complete revascularization.

OBJECTIVES/OBJECTIVE:We aimed to investigate the efficacy and safety of different antithrombotic strategies in patients undergoing transcatheter aortic valve implantation (TAVI) using network meta-analyses. BACKGROUND:Meta-analyses comparing single antiplatelet therapy (SAPT) vs. dual antiplatelet therapy (DAPT), ± oral anticoagulant (OAC) was conducted to determine the appropriate post TAVI antithrombotic regimen. However, there was limited direct comparisons across the different therapeutic strategies. METHODS:MEDLINE and EMBASE were searched through December 2018 to investigate the efficacy and safety of different antithrombotic strategies (SAPT, DAPT, OAC, OAC + SAPT, and OAC + DAPT) in patients undergoing TAVI. The main outcome were all-cause mortality, major or life-threatening bleeding events, and stroke. RESULTS:= 0%). There was no significant difference on stroke among all antithrombotic strategies. CONCLUSION/CONCLUSIONS:Patients who underwent TAVI had similar all-cause mortality rates among different antithrombotic strategies except OAC+DAPT. Patients on SAPT had significantly lower bleeding risk than those on DAPT, OAC + SAPT, and OAC + DAPT. Our results suggest SAPT is the preferred regimen when there is no indication for DAPT or OAC. When DAPT or OAC is indicated, DAPT + OAC should be avoided.